1. Technical Field
The embodiments herein generally relate antibiotics used for a treatment of infectious diseases. The embodiments herein particularly relate to antifungal compounds used for a treatment of infectious diseases such systemic infections in immuno-compromised patients. The embodiments herein more particularly relate to antifungal agents with new mechanism of actions for treating patients with life threatening systemic fungal disease. The embodiments herein also relate to derivatives with an anti-fungal activity, which are capable of inhibiting a biosynthesis of aliphatic amino acid in fungal biological systems. The embodiments herein further relate to a method of synthesizing the newly developed derivatives having an anti-fungal activity. such as aliphatic amino acid biosynthesis inhibitors and a method for determining a mode of action of antifungal compound using reversal assay and molecular techniques
2. Description of the Related Art
Antibiotics are chemical substances with inhibitory or lethal activity on certain organisms. The chemical compositions and the mode of action of antibiotics are diverse. The antibiotics generally exert their inhibitory effects by preventing the cell wall biosynthesis, by inhibiting the protein synthesis, by blocking nucleic acid biosynthesis and through various other unknown mechanisms.
The antibiotics are the essential elements for a successful treatment of any infectious disease. Inspite of their availability, there are still several reasons for exploring the new drugs inevitable. The emergence of drug resistant lethal pathogens has become a significant reason towards the discovery of new drugs. Moreover the significant side-effects of certain drugs coupled with a poor treatment outcome have led to the search for more efficacious and less toxic drugs.
In the recent years, the fungal pathogens have become a major cause of infection in humans with a high mortality rate such as systemic infections in the immuno-compromised patients. A very few number of antifungal drugs are available. However resistant isolates have also been identified. Still there is a need for the antifungal agents with new mechanisms of action for treating the increasing number of patients suffering from the life-threatening systemic fungal diseases. There is also a need to overcome the increasing problems of resistance happening with the current therapies.
The increasing number of fungal resistant against drugs put an emphasis on the significance for searching the new antifungal drugs. Although a screening of natural and chemical sources is one of the main ways for finding the new antifungal combinations. The pharmacology of the combination is important for the pharmaceutical industries. One of the methods for recognizing a reaction mechanism is a reversal assay method. The reversal assay method is performed based on the metabolic mediation capability of a final product of blocked route by the intended drug in deactivating the drug.
About 400 million dollars are annually allocated to an import of the pharmaceutical raw materials to a country. In the last few years, the Scrip journal announced that the maximum rate of sales in two of the greatest pharmaceutical products in Iran is related to antibiotics (24 percent valued at 9.6 million dollar). The antibiotics are the chemical substances which are either taken from the microorganisms like fungi and bacteria or made synthetically. The antibiotics prevent the eukaryotic or prokaryotic cells from living or hinder their proliferation. The components of antibiotics are different depending on the work done by them.
The usage of anti-microbial agents is necessary for a successful treatment of the infectious diseases. Although there are many pharmaceutical categories which are used for treating the infectious diseases in the human beings. The design of the drug and the production of new anti-microbial agents is significant due to several reasons. During the last decade, the resistance in the microorganisms which are considered to be the common pathogens in human beings has been increased. This increase in the resistance has restricted the options of antimicrobial agents which can be used for a treatment of the exclusive organisms. The new antimicrobial agents are also required for a determined group of the microorganisms. A limited number of antimicrobial agents are available for a treatment of the infections caused by fungi. The infections caused by these organisms has created serious concerns.
The fungal pathogens can be divided into two groups called real fungi and opportunistic fungi. The first group is able to harm the human beings naturally. But the second group is mostly seen in those who suffer from immunosuppression, for example, human beings suffering from the diseases such as AIDS, cancer, and organ donation. The fungal infections may be systemic or topical. The systemic infections involve many parts of the body so that they are more significant. Many fungus existing in the nature are superficially harmless. However most of the fungal diseases in the human beings are related to the fungus.
During the last thousand years, many infectious diseases have been discovered and during the last 30 years various new diseases have been discovered. The microorganisms are continuosly changing and finding new places for living and new ways for becoming compatible with the situation. The harmless microorganisms may turn to fatal types and the fatal microorganisms may get transferred from their normal host to the human beings. As the discovery of new infectious diseases continues and new ways and processes of disease by the pathogen agents are created, a production of new antimicrobial agents which are capable of being used for the treatment of these infections seems to be significant. A creation of new pharmaceutical categories with less side effects and shorter therapeutic time for fighting against infectious diseases is of high significance.
Although there are a large number of antibiotics available in the market today but the availability of antifungal antibiotics is very less. However this group of drugs plays an outstanding role in controlling the fungal diseases. Still there are a limited number of antifungal agents currently available for treating the threatening fungal infections.
Although there have been more options for the antifungal drugs against the fungal infections in the last thirty years, the pharmacologic principles of an antifungal treatment are not thoroughly recognized. An estimation of a therapeutic concentration of the antifungal drugs would be difficult without achieving any reasonable results from a concentration of a drug required for ceasing a growth of fungus in a laboratory environment.
Although the screening of various chemical or natural libraries has been a useful approach for a discovery of the new antifungal compounds their mode of action is important for the pharmaceutical industries. There are new pharmaceutical molecules that do not enjoy any ideal feature but they are capable of achieving the desirable stages and they can be optimized during a drug development process. The mode of action (MOA) of many of the antimicrobial drugs is totally unrecognized since an elucidation mechanism of many of them is difficult and undetectable. In many cases, a complicated mechanism is applied for the antibiotics for an instant and an intensive effect on an intended cell.
Hence there is a need to develop a method for determining a mechanism of action of the anti-fungal drugs. Also there is a need to utilize these methods for developing the anti-resistant drugs where the determined mechanism of action of the anti-fungal drugs is used to overcome a resistance caused to the antifungal drugs by the fungus. Further there is a need to develop the anti-fungal agents or combinations that work by inhibiting a synthesis of the aliphatic amino acids in the fungus thereby inhibiting their growth.
The above mentioned shortcomings, disadvantages and problems are addressed herein and which will be understood by reading and studying the following specification.